Guest guest Posted September 8, 2004 Report Share Posted September 8, 2004 > 7 Sep 2004 19:05:58 -0000 > Caring Mothers Reduce Response to Stress > for Life > press-release > > > The Institute of Science in Society Science Society > Sustainability http://www.i-sis.org.uk > > General Enquiries sam Website/Mailing > List > press-release ISIS Director > m.w.ho > ======================================================== > > Life after the Central Dogma > > The biotech industry was launched on the scientific > myth > that organisms are hardwired in their genes, a myth > thoroughly exploded by scientific findings > accumulating > since the mid 1970s and especially so since genome > sequences > have been accumulating (see Living with the Fluid > Genome > http://www.i-sis.org.uk/fluidGenome.php, by Mae-Wan > Ho ). We > bring you the latest surprises that tell you why our > health > and environmental policies based on genetic > engineering and > genomics are completely misguided; and more > importantly, why > the new genetics demands a thoroughly ecological > approach. > > Death of the Central Dogma > http://www.i-sis.org.uk/DCD.php > Caring Mothers Reduce Response to Stress for Life > http://www.i-sis.org.uk/MCDIRTS.php > > > > ISIS Press Release 07/09/04 > Caring Mothers Reduce Response to Stress for Life > ********************************* > > How a rat responds to stress depends on whether its > mother > cared for it properly as a pup, which marks its > genes for life. > Dr. Mae-Wan Ho reports > > References ( > http://www.i-sis.org.uk/full/MCDIRTSFull.php ) > for this article are posted on ISIS members' > website. > Details here > (http://www.i-sis.org.uk/membership.php) > > Maternal effects in the spotlight > > Maternal effects on the development of offspring are > well > known. But they are thought to be due to nutritional > and > physiological factors affecting the foetus in the > womb; and > within the past few years, geneticists have > discovered that > diet and stress can profoundly change the pattern of > gene > expression in the offspring, affecting their health > prospects as adults (see Diet trumping genes, SiS 20 > > http://www.i-sis.org.uk/isisnews/sis20.php). > > A team of researchers from the Douglas Hospital > Research > Centre and McGill University in Montreal Canada, and > the > Molecular Medicine Centre, in Edinburgh University > Western > General Hospital in the UK, now report a remarkable > experiment in which the behaviour of the mother > nursing her > pups not only affects the pups' response to stress > as > adults, but are correlated with changes in gene > expression > states in brain cells that persist into adult life. > Such > changes are referred to as 'epigenetic' as they do > not > involve alterations in the base sequence of DNA in > the > genome, only their off and on states; but they can > persist > in the brain cells and are passed on to all the > daughter > cells. > > Caring mothers reduces stress response of pups > > In the nest, the mother rat licks and grooms her > pups, and > while nursing, arches her back to groom and lick her > pups. > Some mothers (high performers) tend to do these more > > frequently than others (low performers). As adults, > the > offspring of high performers are less fearful and > show more > modest responses to stress in the > hypothalamus-pituitary- > adrenal (HPA) neuro-endocrine pathway. > > Cross-fostering studies showed that the biological > offspring > of low-performers reared by high-performers, > resemble the > offspring of high performers, and vice versa. > Maternal > behaviour, therefore, alters the development of the > HPA > responses to stress. The magnitude of the HPA > response is a > function of the corticotropin-releasing factor (CRF) > > secreted by the hypothalamus, which activates the > pituitary- > adrenal system. This is modulated by glucocorticoid, > which > feeds back to inhibit CRF synthesis and secretion, > thus > dampening the HPA responses to stress. The adult > offspring > of high-versus low performer mothers show increased > glucocorticoid expression the hippocampus, and > enhanced > sensitivity to glucocorticoid feedback. If this > difference > is eliminated, so is the difference in HPA responses > to > stress. > > Maternal care and gene expression > > Previous studies indicate that the maternal > behaviour of > licking and grooming and arching her back to do so > while > nursing increased the expression of glucocorticoid > receptor > (GR), accompanied by, among other things, an > increased > expression of a special transcription factor, > NGF1-A, which > binds to the promoter of the GR gene to increase its > > transcription and expression. But how could this be > transmitted from the neonate to the adult? > > The answer is: through the structure of chromatin > (complex > of protein and DNA in the chromosomes), and the > methylation > of DNA. DNA methylation is a stable chemical > modification of > the cytosine in the cytosine-guanine (CpG) > dinucleotides, > often associated with stable variations in gene > transcription. Under-methylation of CpG > dinucleotides is > associated with active transcription. The > researchers > decided to look at the methylation state of the GR > promoter > around the binding region of the NGF1-A > transcription factor > in the hippocampus of adult offspring from high and > low > performers. Sure enough, they found highly > significant > differences in methylation, with low methylation in > offspring from high-performing mothers and high > methylation > in offspring from low-performing mothers, > corresponding to > high and low expression respectively of the GR. > > Cross-fostering results in methylation patterns > associated > with the adoptive mother, as consistent with the > change in > the adult offspring's responses to stress. Moreover, > these > epigenetic differences due to maternal behaviour > during the > first week of life persisted into adulthood. > > A clean slate at birth > > Amazingly, the pups of both high and low-performing > mothers > start out life genetically the same. Just before > birth, the > entire region of the GR promoter was unmethylated in > both > groups; and day one after birth, methylation is > found in the > region in both groups to the same extent. > > The changes in methylation pattern then develops > within the > first week according to the behaviour of the mother, > and > thereafter remain for the rest of their lives. This > finding > is consistent with earlier studies showing that the > first > week of postnatal life is a 'critical period' for > the > effects of early experiences on hippocampus GR > expression. > The hippocampus is the 'emotion centre' of the > brain, and is > believed to be responsible for transferring memory > to the > rest of the brain. It is vulnerable to stress and > richly > supplied with receptors for the sex hormones [2, 3]. > > > Additional markings of the gene > > Next, the researchers looked at the structure of > chromatin > around the GR gene, as chromatin structure > determines > whether a gene is transcribed or not. Chemical > modification > of the histones (major chromatin protein) by adding > an > acetyl- group is a well-established marker for > 'active' > chromatin around transcribed genes, which makes it > accessible for the transcription enzyme complex. > Again, they > found highly significant changes in acetylation > between the > two groups of pups. There was greater acetylation > and > threefold greater binding of the NGF1-A > transcription factor > to the GR promoter in the adult offspring of high- > compared > with low-performing mothers. > > Marked for life? > > Now, a critical question is, are these gene-marking > changes > reversible? Is the adult doomed to conditioning by > the > mother's behaviour towards it as a pup? The general > belief > is that one is marked for life. DNA methylation > pattern is > irreversible. However, recent data from in vitro > experiments > suggests that under certain circumstances, it is > possible to > demethylate DNA by increasing histone acetylation > through a > chemical inhibitor of the deacetylating enzyme, > trichostatin > A (TSA). The researchers, rather crudely, infused > the adult > brain with TSA by applying the solution into the > ventricle > (space inside the brain), and obtained more than > 3-fold > binding of the NGF1-A protein to the GR promoter in > the > adult offspring of low-performers, and as expected, > no > change in the adult offspring of high-performers. > Simultaneously correlated changes in DNA methylation > pattern > of the GR promoter was found in the adults reared by > low- > performing mothers treated with TSA, but not those > reared by > high-performing mothers. In other words, those > epigenetic > changes were reversed. > > The next question is, are the reversal of epigenetic > changes > associated with reversal in HPA responses to stress? > The > answer, incredibly, is yes. The TSA treatment, crude > as it > was, appeared to significantly decreased plasma > corticosterone in the offspring of low-performer in > response > to stress. > > This is all grist to the mill of the fluid and > adaptive, > adaptable genome [4] that makes nonsense of the > Central > Dogma. mail message here > > > ======================================================== > > This article can be found on the I-SIS website at > http://www.i-sis.org.uk/MCDIRTS.php > > If you like this original article from the Institute > of > Science in Society, and would like to continue > receiving > articles of this calibre, please consider making a > donation > or purchase on our website > > http://www.i-sis.org.uk/donations. > > ISIS is an independent, not-for-profit organisation > dedicated to providing critical public information > on > cutting edge science, and to promoting social > accountability > and ecological sustainability in science. > > If you would prefer to receive future mailings as > HTML > please let us know. If you would like to be removed > from our > mailing list at > > http://www.i-sis.org.uk/mailinglist/.php > ======================================================== > > CONTACT DETAILS > > The Institute of Science in Society, PO Box 32097, > London > NW1 OXR > > telephone: [44 20 8643 0681] [44 20 7383 3376] > [44 20 > 7272 5636] > > General Enquiries sam Website/Mailing > List > press-release ISIS Director > m.w.ho > > MATERIAL IN THIS EMAIL MAY BE REPRODUCED IN ANY FORM > WITHOUT > PERMISSION, ON CONDITION THAT IT IS ACCREDITED > ACCORDINGLY > AND CONTAINS A LINK TO http://www.i-sis.org.uk/ Quote Link to comment Share on other sites More sharing options...
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